UNITED STATES OF AMERICA
FOOD AND DRUG ADMINISTRATION
CENTER FOR DRUG EVALUATION AND RESEARCH
* * *
NONPRESCRIPTION DRUGS ADVISORY COMMITTEE (NDAC)
IN JOINT SESSION WITH THE
ADVISORY COMMITTEE FOR REPRODUCTIVE HEALTH DRUGS (ACRHD)
* * *
MEETING
* * *
TUESDAY,
DECEMBER 16, 2003
The
joint Advisory Committees met at 8:00 a.m in the Grand Ballroom of the
Gaithersburg Hilton, 620 Perry Parkway, Gaithersburg, Maryland, Dr. Louis
Cantilena, Jr., NDAC Chairman, presiding.
PRESENT:
LOUIS R. CANTILENA, Jr., M.D., Ph.D., NDAC
Chairman
LINDA C. GIUDICE, M..D., Ph.D., ACRHD Chair
MICHAEL C. ALFANO, D.M.D., Ph.D., Acting Industry
Representative
PRESENT (Continued):
NEAL L. BENOWITZ, M.D., NDAC
ABBEY B. BERENSON, M.D., Consultant (Voting)
TERRENCE F. BLASCHKE, M.D., NDAC
LESLIE CLAPP, M.D., NDAC
SUSAN A CROCKETT, M.D, ACRHD
FRANK F. DAVIDOFF, M.D., NDAC
SCOTT S. EMERSON, M.D., Ph.D., ACRHD
MICHAEL F.
GREENE, M.D., Consultant (Voting)
W. DAVID HAGER, M.D., ACRHD
GERI D. HEWITT, M.D., Consultant (Voting)
JULIE A. JOHNSON, Pharm.D., NDAC
Y.W. FRANCIS LAM, Pharm.D., NDAC
VIVIAN LEWIS, M.D., ACRHD
LARRY LIPSHULTZ, M.D., ACRHD
CHARLES J. LOCKWOOD, M.D., ACRHD
GEORGE A. MACONES, M.D., ACRHD
SONIA PATTEN, Ph.D., NDAC Consumer Representative
VALERIE MONTGOMERY RICE, M.D., ACRHD
WAYNE R. SNODGRASS, M.D., Ph.D., NDAC
JOSEPH STANFORD, M.D., ACRHD
MARY E. TINETTI, M.D., NDAC
PRESENT (Continued):
JAMES TRUSSELL, Ph.D., Consultant (Voting)
LORRAINE TULMAN, RN, M.S., ACRHD Consumer
Representative
DONALD L. UDEN, Pharm.D., NDAC
HENRY W. WILLIAMS, Jr., M.D., NDAC
ALASTAIR WOOD, M.D., NDAC
KAREN M. TEMPLETON-SOMERS, Ph.D., NDAC Executive
Secretary
SPONSOR REPRESENTATIVES AND CONSULTANTS:
CAROLE BEN-MAIMON, M.D.
VIVIAN DICKERSON, M.D.
DAVID GRIMES, M.D.
FDA REPRESENTATIVES:
STEVEN K. GALSON, M.D., M.P.H., Acting Director,
CDER
SANDRA KWEDER, M.D., Deputy Director, OND
JONCA BULL, M.D., Director, ODE V
JULIE BEITZ, M.D., Deputy Director, ODE III
DONNA GRIEBEL, M.D., Deputy Director, DRUDP
CURTIS J. ROSEBRAUGH, M.D., M.P.H., Deputy
Director, DOTCDP
ANDREA LEONARD SEGAL, Team Leader,
JIN CHEN, M.D., Ph.D., Medical Officer, DOTCDP
DANIEL DAVIS, M.D., M.P.H., Medical Officer,
DRUDP
KAREN LECHTER, J.D., Ph.D., Social Science
Analyst, DSRCS
C O N T E N
T S
Introductions .................................... 6
Conflict of Interest Statement .................. 12
Opening Remarks, Dr. Sandra Kweder .............. 13
Introduction to the Issues, Dr. Curtis
Rosebraugh
................................ 20
Sponsor Presentation:
Dr.
Carole Ben-Maimon ............. 26,
40, 64
Dr.
Vivian Dickerson ...................... 33
Dr.
David Grimes .......................... 59
FDA Presentation:
Dr.
Daniel Davis .......................... 98
Dr.
Karen Lechter ........................ 114
Dr.
Jin Chen ............................. 124
Open Public Hearing:
Dr.
Melanie Gold ......................... 155
Dr.
Vanessa Cullins ...................... 157
Dr.
Gretchen Stuart ...................... 160
Delegate
Bob Marshall .................... 162
Rachel
Laser ............................. 165
Dr.
Felicia Stewart ...................... 167
Wendy
Wright ............................. 169
Linda
Freeman ............................ 171
Carole
Denner ............................ 176
Erin
Mahoney ............................. 179
Teresa
Harrison .......................... 180
Dr.
Hanna Klaus .......................... 182
Kirsten
Moore ............................ 185
Dr.
Beth Jordan .......................... 185
Dr.
Robert Carroll ....................... 188
Dr.
Janet Engle .......................... 189
Hillary
Flowers .......................... 192
Kelly
Mangan ............................. 194
Dr.
John Bruchalski ...................... 195
Dr.
Chris Kahlenborn ..................... 197
Dr.
Daniel Hussar ........................ 199
Heather
Boonstra ......................... 202
C O N T E N T S
(Continued)
PAGE
Open Public Hearing (Continued):
Dr.
William Colliton ..................... 204
Karen
Coleman ............................ 206
Alexandra
Leader ......................... 208
Amy
Allina ............................... 210
Judie
Brown .............................. 212
Stephanie
Seguin ......................... 214
Jane
Boggess ............................. 216
Silvia
Henriquez ......................... 218
Vera
Brown ............................... 220
Carol
Petraitis .......................... 222
Erika
Gubrium ............................ 224
Jill
Stanek .............................. 226
Kim
Gandy ................................ 228
Deven
McGraw ............................. 230
Andre
Ulmann ............................. 232
Dr.
Erin Gainer .......................... 233
Candi
Churchill .......................... 235
Jennifer
Taylor .......................... 238
Rev.
Robert Tiller ....................... 240
Dr.
Albert George Thomas ................. 242
Clarifying Questions from Committee ............ 246
Question for the Committee ..................... 301
P R O C E E D I
N G S
(8:05
a.m.)
CHAIRMAN
CANTILENA: Good morning, everyone. We'd like to get started.
I'd
like to welcome you to the December 16th, 2003, meeting of the Nonprescription Drugs Advisory Committee and
jointly with the Reproductive Health Drugs Advisory Committee.
We're
here today to discuss the proposition of switching Plan B from Rx to
over-the-counter, and before we get started, Dr. Somers has a statement that
she needs to read for all of us.
DR.
TEMPLETON-SOMERS: Good morning, and
welcome to this joint session of the Nonprescription Drugs Advisory Committee
and the Advisory Committee for Reproductive Health Drugs.
All
committee members have been provided with copies of background materials from
both the sponsor and the FDA and with copies of the letters from the public
that were received by the December 5th deadline. The background materials were posted on the
FDA Web site yesterday morning.
Copies
of all of these materials are available for viewing only at the FDA desk
outside this room.
Today
we have a very large table, a full house, and an exciting topic. So we'd like to start with a few rules of
order.
FDA
relies on its advisory committees to provide the best possible scientific
advice available to assist us in making complex decisions. We understand that issues raised during the
meeting may well lead to conversations over breaks or during lunch.
However,
one of the benefits of an Advisory Committee meeting is that the discussions
take place in an open and public forum.
To that end, we request sincerely that members of the committee not
engage in private, off-record conversations or interviews on today's topic
during the breaks or during lunch.
Whenever
there is an important topic to be discussed, there are a variety of
opinions. One of our goals today is for
this meeting to be conducted in a fair and open way where every participant is
listened to carefully, treated with dignity, courtesy, and respect. Anybody whose behavior is disruptive to the
meeting will be asked to leave.
We
are confident that everyone here is sensitive to these issues and can
appreciate that these comments are intended as a gentle reminder. We look forward to a productive and
interesting meeting.
Thank
you.
CHAIRMAN
CANTILENA: Okay, and as I said earlier,
my name is Dr. Lou Cantilena, head of clinical pharmacology at the Uniformed
Services University. I'll be chairing
this meeting.
And
we'd like to go around so that everyone can introduce themselves, and we'll
start on this side.
DR.
ALFANO: Michael Alfano, Dean of the
Dental School at New York University.
DR.
HAGER: David Hager, Reproductive Health
Drugs, from the University of Kentucky.
DR.
LAM: Francis Lam from University of
Texas Health Science Center in San Antonio, a member of NDAC.
DR.
LIPSHULTZ: Larry Lipshultz, Professor of
Urology, Baylor College of Medicine.
DR.
JOHNSON: Julie Johnson from University
of Florida Colleges of Pharmacy and Medicine, from the Nonprescription Drug
Committee.
DR.
MACONES: George Macones. I'm Associate Professor of OB-GYN and
Epidemiology at the University of Pennsylvania on Reproductive Drugs.
DR.
PATTEN: Sonia Patten. I'm a consumer representative. I'm an anthropologist on faculty at
Macalester College in St. Paul, Minnesota, and I'm part of the Nonprescription
Drug Committee.
DR.
CROCKETT; I'm Susan Crockett. I'm a general OB-GYN Director of Maternity
Services for the CHRISTUS Santa Rosa Family Practice Residency Program, and I'm
a member of the Reproductive Health Drugs Committee.
DR.
UDEN: I'm Don Uden, a professor at the
University of Minnesota College of Pharmacy and member of NDAC.
DR.
STANFORD: Joseph Stanford, University of
Utah, Department of Family and Preventive Medicine on the Reproductive Health
Drugs Committee.
DR.
BENOWITZ: Neal Benowitz. I'm an internist and clinical pharmacologist
from U.C., San Francisco, on the Nonprescription Drug Committee.
DR.
LOCKWOOD: Charles Lockwood, Chair of
OB-GYN at Yale and Reproductive Drugs.
MS.
TULMAN: Lorraine Tulman, Associate
Professor, University of Pennsylvania School of Nursing, Reproductive Health
Advisory Group, and I'm the consumer representative for that group.
DR.
TRUSSELL: James Trussell from the Office
of Population Research at Princeton University.
DR.
GIUDICE: Linda Giudice, reproductive
endocrinologist and Professor of OB-GYN at
Stanford University, and Chair of
the Reproductive Health Drugs Committee.
DR.
TINETTI: Mary Tinetti, Department of
Medicine, Yale, Nonprescription Drug Committee.
DR.
HEWITT: I'm Geri Hewitt, Assistant
Professor of the Department of OB-GYN and Department of Pediatrics at Ohio
State College of Medicine.
DR.
GREENE: I'm Michael Greene, Professor
of Obstetrics, Gynecology and Reproductive Biology at Harvard Medical School.
DR.
CLAPP: Leslie Clapp, pediatrician,
Buffalo, New York, and Clinical Associate Professor of Pediatrics, University
of Buffalo.
DR.
SNODGRASS: Wayne Snodgrass, Department
of Pediatrics, University of Texas in Galveston, and clinical pharmacology on
the Nonprescription Drug Committee.
DR.
LEWIS: Vivian Lewis, Professor of OB-GYN
at University of Rochester, and I'm on the Reproductive Health Drugs Committee.
DR.
BLASCHKE: Terry Blaschke,
internist/clinical pharmacologist, Stanford.
DR.
WOOD: I'm Alastair Wood from Department
of Medicine, Department of Pharmacology at Vanderbilt, and I'm on NDAC.
DR.
EMERSON: Scott Emerson, Professor of
Biostatistics at the University of Washington on Reproductive Drugs.
DR.
BERENSON: Abbey Berenson, Professor of
OB-GYN and Pediatrics at University of Texas Medical Branch at Galveston.
DR.
DAVIDOFF: I am Frank Davidoff. I'm the editor emeritus of the Annals of
Internal Medicine; also now the executive editor at the Institute for
Health Care Improvement, and I'm on the NDAC.
DR.
MONTGOMERY: Valerie Montgomery Rice,
Professor and Chair of Obstetrics and Gynecology, Meharry Medical College, and
I'm on the Reproductive Health Drugs.
DR.
GRIEBEL: Donna Griebel, Deputy, Division
of Repro. and Urologic Drug Products, FDA.
DR.
ROSEBRAUGH: Curt Rosebraugh, Deputy of
Over-the-Counter Drug Products.
DR.
BEITZ: Julie Beitz, Deputy Director,
Office of Drug Evaluation III, CDER, FDA.
DR.
BULL: Good morning. Jonca Bull, the Director of the Office of
Drug Evaluation IV in CDER, FDA.
DR.
GALSON: Steve Galson. I'm the Acting Director of the Center for
Drug Evaluation and Research.
DR.
KWEDER: I'm Sandra Kweder. I'm the Deputy Director of the Office of New
Drugs in CDER.
DR.
TEMPLETON-SOMERS: Thank you. I'm Karen Templeton-Somers, Executive
Secretary to the Committee, FDA.
And
the following announcement addresses conflict of interest issues with respect
to this meeting and is made a part of the record to preclude even the
appearance of impropriety at the meeting.
The
conflict of interest statutes prohibit special government employees from
participating in matters that could affect their own or their employer's
financial interests. All participants
have been screened for interests related to the product, competing products and
companies that could be affected by today's discussions The agency has reviewed the interests
reported by the committee participants and has determined that there is no
potential for a conflict of interest at this meeting.
We
would like to disclose that Dr. Michael Alfano is participating as the acting
industry representative, acting on behalf of Regulated Industry.
In
the event the discussions involve any other products or firms not already on
the agenda for which FDA participants have a financial interest, the
participants are aware of the need to exclude themselves from such involvement,
and their exclusion will be noted for the record.
With
respect to all other participants, we ask in the interest of fairness that they
address any current or previous financial involvement with any firm whose
products they may wish to comment upon.
Thank
you.
CHAIRMAN
CANTILENA: Thank you, Dr. Somers.
We'll
now hear from Dr. Sandy Kweder, who will open the meeting for the FDA.
DR.
KWEDER: Well, good morning, everyone,
and welcome. I'd first like to start off
the meeting by acknowledging the large size of the panel today and thanking all
of you on the panel for coming here.
Sometimes a large panel makes interchange more difficult, but I think
Dr. Cantilena is probably up to the challenge.
Your
discussion is extremely important to us, but before you begin that, I'd like to
provide some background perspective as to how we got here.
Following
my remarks, Dr. Curt Rosebraugh will introduce the subject in more detail and
get on with some of the scientific presentations.
First,
let me be clear that we're here today to discuss the scientific data available
to address Barr Lab's application to remove the prescription requirement for
their product Plan B. Plan B is an
emergency contraceptive that is indicated for use in the unexpected
circumstance when another standard contraceptive method fails or fails to be
used.
While
previously established safety and efficacy data for this medication will be
referenced, you'll be asked to consider these data only as they relate to Plan
B's suitability for nonprescription status.
You'll hear a lot more about FDA's general approach to making decisions
about switches from prescription to nonprescription status. So I'm not going to address that further.
But,
secondly, I would like to assure you that we at FDA recognize the broad array
of issues related to emergency contraception, in general, that may arise in
your discussion. None of these are new.
In
June of 2000, FDA, CDER particularly, held a Part 15 hearing. The purpose of that two-day hearing was
solely to solicit public testimony on the future of prescription to
nonprescription product shifts. We
requested that experts and any concerned member of the public come and share
their perspectives in several areas.
What
products should and should not be considered for nonprescription status?
What
are the perceived incentives and perceived barriers to such shifts?
And
outstanding issues, what are they that might be addressed to modify incentives
and barriers?
I
was part of the FDA panel listening to that testimony. In addition to other product groups
discussed, like cholesterol lowering agents, non-sedating antihistamines and
antihypertensives, we heard several hours of testimony regarding oral
contraceptives as potential candidates for being available without a
prescription, but in particular, many speakers favored or did not favor making
emergency contraception nonprescription.
Those
in the favoring group pointed out that the clinical safety of the product and
the importance of access to emergency contraception are the keys to maximizing
its effectiveness. For example, if the
product is to be used as directed, the woman must be able to take it within 72
hours of intercourse. This is often not
achievable given our current system of pharmacy practice.
They
also cited studies in the literature which showed that women do not appear to
substitute emergency contraception for other more traditional forms of
contraception.
Those
who did not favor nonprescription status raised public health concerns about
potential effects of wider availability of the product on adolescent health and
behavior. For example, these speakers
did not find the published literature convincing with regard to the impact of
more readily available emergency contraceptives on adolescent behavior. Of particular concern to them were whether
nonprescription access would increase sexually transmitted infections and
decrease the use of other more effective contraceptives or even affect choices
about sexual behavior in adolescent groups.
We
at FDA understand the complexity and the multiple perspectives on these
matters. We will consider their full
breadth before arriving at any final regulatory decision following this
meeting.
Finally,
I want to say a few words about seeking answers to difficult questions and
decision making. One of the things that
we at FDA do when we're faced with one is we often look to others' experiences
to see what has happened with those who have gone before us.
For
example, we look to the experience of products as they may be marketed in other
countries. Some of those experiences may
come up today in the presentations and your discussions. You may be reassured by these or frustrated
because there are not detailed data to answer questions you might like to have
addressed.
Please
keep in mind that considering the effects of nonprescription or prescription
medicines in countries other than the United States is fraught with challenges
of interpretation because of differences in pharmacy models.
For
example in some countries having things, what might be called behind the
country, only means that a person has to ask for them. For example, in those countries this status
is applied to hundreds of medicines. The
open shelves in the shop are there only for toiletries and other supplies.
In
these countries, including many in Europe, most of the products that we
routinely consider over-the-counter and readily available even in a grocery
store are distributed in this manner at a pharmacist's counter, as are many
products that we are used to only having available by prescription.
In
other countries, the term "behind the counter" refers to the need to
request the product of a pharmacist and obtain or have the opportunity to be
counseled by a pharmacist.
The
bottom line is that data from these countries can only be looked at from an
arm's length, and they do not necessarily translate into data that give solid
answers to bigger picture questions that we or you may have. We just have to do the best we can.
Again,
thank you for coming and for your willingness to help us with a challenging
decision. Discussions at these meetings
are as important, if not more important, than any vote tally on the formal
questions that we pose, and we're looking forward to your discussion today.
Thank
you.
CHAIRMAN
CANTILENA: Okay. Thank you, Dr. Kweder.
Dr.
Rosebraugh, would you like to continue with the FDA introduction, please?
DR.
ROSEBRAUGH: Good morning. On behalf of the Divisions of Over-the-Counter
Drug Products and Reproductive and Urologic Drug Products, I'd like to welcome
the members of each respective Advisory Committee to today's meeting regarding
the nonprescription status of Plan B.
By
way of introduction, I would like to briefly go over the regulatory history of
Plan B, go over the regulatory requirements for nonprescription marketing of
drug products, and outline today's agenda.
Plan
B was approved for prescription use on July 28th, 1999, for the indication as
an emergency contraception to be used to prevent pregnancy following
unprotected intercourse or a known or suspected contraceptive failure. Prescription directions for use indicate that
to obtain optimal efficacy, the first does needs to be taken as soon as
possible within 72 hours of intercourse, and the second dose needs to be taken
12 hours later.
Women's
Capitol Corporation, the applicant for the original prescription NDA, submitted
an application for Plan B switch from prescription to nonprescription status in
April of 2003. As the efficacy of Plan
B, when used as per directed has already been established and the sponsor is
not seeking a new indication or dosage regimen, this will not be a topic at
today's meeting.
However,
the efficacy based on a use in a nonprescription setting is of interest to
us.
The
purpose of today's Advisory Committee meeting is to determine whether Plan B
meets regulatory requirements for nonprescription marketing.
Regarding
nonprescription requirements or requirements for nonprescription marketing, the
Durham-Humphrey Amendment to the Federal Food, Drug, and Cosmetic Act, which
was enacted in 1951, formally differentiates between prescription and
nonprescription drugs. This is
articulated in the Code of Federal Regulations 21 CFR 310-200(b) and states,
"Any drug limited to prescription use under Section 503(b)(1)(C) of the
Act shall be exempt from prescription dispensing requirements when the
Commissioner finds such requirements are not necessary for the protection of
public health by reason of the drug's toxicity or other potentialities for
harmful effects, the method of its use, or the collateral measures necessary to
its use, and he finds that the drug is safe and effective for use in
self-medication as directed in the proposed labeling."
So
the bottom line is this regulation provides that a drug be sold nonprescription
if it is safe and if adequate directions for use can be written that are
discernable to a lay person.
When
approaching a possible prescription to nonprescription switch candidate, there
are several questions that the agency takes into consideration to assess
whether the product is, indeed, a suitable switch candidate. Regarding the questions that we take into
consideration, we wonder if the product has an acceptable safety margin, as
demonstrated from prior prescription marketing experience; whether it has low
misuse and abuse potential, a reasonable therapeutic index of safety; whether
the condition that it is being used for can be adequately self-recognized and
self-treated with minimal health care provider intervention; whether the
benefits outweigh the risks; and when the product used under nonprescription
conditions, is it safe and effective?
If
the answer to the above questions are yes, then the proposed product may meet
regulatory requirements for nonprescription safety and effectiveness and is a
candidate for consideration of nonprescription marketing.
In
order to address the questions that face switch candidates, the Plan B switch
NDA application components included summaries from previously existing data and
newly conducted studies. To address the
safety profile and misuse and abuse potential of the product, the sponsor has
submitted safety data from their original NDA and a review of post marketing
safety, both foreign and domestic, and a review of the published literature.
To
evaluate consumers' ability to self-recognize the condition they are treating
and whether self-treatment with the product is safe, the sponsor has conducted
label comprehension and actual use studies.
We will be hearing greater detail about these things during this
morning's presentations.
This
type of data and the studies that the sponsor has performed are consistent with
other submissions that have been evaluated in the past where the switch did not
involve a change in dosage or indication.
To
review today's agenda, we will begin with a presentation by the sponsor, and
that will be followed by a question and answer session.
Then
following a break, we will have presentations by the FDA. Dr. Dan Davis will be presenting the FDA's
review of safety. Dr. Karen Lechter will
be presenting the FDA's review of the label comprehension study, and Dr. Jin Chen
will be presenting the FDA's review of actual use studies and the literature
review.
That
will then be followed by a question and answer session of the FDA.
We
will then have an open public hearing, then a much deserved lunch, and finally
we will dedicate the afternoon to the panel discussion.
During
the presentations the joint committee members should consider the information
and use the question and answer session to prepare to answer the questions
posed to the committee regarding the possible prescription-to-nonprescription
switch of Plan B.
With
that as a background, the agency looks forward to today's discussion.
CHAIRMAN
CANTILENA: Thank you, Dr. Rosebraugh.
Okay. At this time we will move to the sponsor presentation, which will
be led by Dr. Ben-Maimon from Barr.
Dr.
Maimon, if you would start and then as you go through you can introduce the
other members of your team.
For
the committee, we'll hold our questions until the end of sponsor presentation.
Thank
you.
DR.
BEN-MAIMON: Good morning,
everybody. I'd like to start by just
thanking the panel, the FDA, for giving us this opportunity to present the data
supporting the prescription to over-counter switch. We're all very interested, as the FDA stated,
in hearing the panel's discussion and comments, and of course, interested in
answering as many of the questions as we possibly can.
I'm
Carole Ben-Maimon, President/COO of Barr research.
You
may have heard that Barr Laboratories has signed a letter of intent to acquire
the assets of Women's Capitol Corporation.
That includes Plan B for emergency contraception. That transaction has not yet closed, and so
today I'm actually representing Women's Capitol Corporation.
A
little bit about what I'm going to cover in the presentation today. First, the background, a little bit of an
overview, and a discussion about how Plan B prevents pregnancy. I'll talk a little bit about the rationale
for the over-the-counter switch, try and not duplicate what was already said,
and then I'm going to turn the podium over to Dr. Vivian Dickerson, who is the
President-elect for the American College of Obstetricians and Gynecologists,
for her to discuss with you the benefit-risk assessment as ACOG sees it.
I'll
return to the podium and give you some background on our clinical trials, the
label comprehension and actual use, and then Dr. David Grimes, Vice President
of Biomedical Affairs at Family Health International and clinical professor at
the Department of Obstetrics and Gynecology at the University of North Carolina
School of Medicine, will give a presentation and discuss the health
consequences of an OTC switch for Plan B.
Finally,
I'll return to the podium and discuss with you our CARE Program, which many of
you saw in the briefing document. That
program is really designed to increase access and awareness, as well as
availability of Plan B, and I'll discuss some of the rationale and the
presentation for that.
What
is emergency contraception? Emergency
contraception is therapy for women who desire prevention of pregnancy, have had
unprotected sexual intercourse, including contraceptive failures and sexual
assault.
It's
really important that we look at this in the context of what's going on in this
country today. Fifty-three percent of
unintended pregnancies occur in women who are using contraceptives. These are method failures or user failures,
condoms that break, slip, women who miss their pills, but clearly, 53 percent
of the unintended pregnancies are in women who have been using contraceptives.
Unplanned
pregnancies are a major health care problem in this country. There are over three million unintended
pregnancies in the United States each year.
With typical use, 15 percent of women who are using condoms will be
become pregnant each year and eight percent of those using oral contraceptives
will become pregnant each year.
Half
of the unintended pregnancies in this country will result in abortion. It is estimated that up to 50 percent of
these pregnancies could be prevented with greater access and use of emergency
contraception.
There
are two approved products today in the United States: Preven, which was approved in 1998, and Plan
B, which you already heard was approved in 1999.
I
hope they're not putting you to sleep.
Preven
is a combination product with an ethinyl estradiol, and Plan B is actually just
a levonorgestrel product, a progestin only product, and that's really of
significance as we get into how these products prevent pregnancy.
But
you can see that the regimens are essentially identical. Both have to be taken within 72 hours of the
active unprotected sexual intercourse, and the second tablet has to be taken 12
hours later.
The
most fertile days of the female cycle, the menstrual cycle, are the five days
leading up to ovulation and then 24 hours after, and within 24 hours of ovulation,
the egg is no longer viable and fertilization cannot occur.
Plan
B works like other progestin only oral contraceptives and prevents
ovulation. Plan B is an oral
contraceptive, not an abortion pill. The
direct evidence is highly in favor of the fact that the primary mechanism of
action, if not the sole mechanism of action, is prevention of ovulation.
There
are two hypothetical mechanisms that have been proposed: interference with fertilization and
interference with implantation, but for levonorgestrel only contraceptives,
levonorgestrel only emergency contraceptives, there is no data to suggest that
either of these are impacted, either of these events are affected by Plan B.
Again,
I would reiterate Plan B works by preventing ovulation. It is an oral contraceptive, not an abortion
pill.
What's
really critical when we consider the over-the-counter switch of Plan B is this
chart, and what this is is the data from the efficacy trial that was included
in the original NDA that supported the approval of the prescription drug
product, and this was the WHO study that was done in the late '90s.
And
what it shows is that if Plan B, if the first tablet is taken within 24 hours
of the active unprotected sex, the pregnancy rate is as low as .4 percent. Many of you may know that with a single act
of mid-cycle sex the pregnancy rate is about eight percent. So clearly, the reduction is significant
within the first 24 hours.
If
a woman waits until 48 to 72 hours, the pregnancy rate rises to 2.7 percent. It is imperative that women have access to
this product quickly so that they can maximize its effect.
What
does the prescription requirement do?
Well, it creates delays. The
woman needs to identify the need, clearly a need that is easily identified by
most women given the fact that they have either had a contraceptive failure,
coercive sex or rape, or unprotected sex.
They
need to then locate a prescriber who is willing to prescribe emergency
contraception for them. Again, we can't
forget that most of these events are not occurring between nine to five Monday
to Friday. They're occurring at night
and on weekends, and so this is not always an easy undertaking.
They
have to call the prescriber. They have
to talk to the prescriber. The
prescriber then has to call them back and decide to prescribe the product.
If
a woman does not have a physician that she sees regularly or somebody that
follows her regularly, the doctor may want for them to come into the office and
be examined because clearly, doctors are reticent sometimes to calling in
prescriptions to patients who they don't know and probably for good reason.
And
so once she gets her prescription, she now has to go to pharmacy, and at the
pharmacy I can tell you and will show you data to support this, not a lot of
pharmacies stock this product, and the reason is the volume and the demand are
quite low to date because awareness is low.
So just finding a pharmacy where she can obtain the product in a timely
fashion can also be a challenge.
And
finally, she can purchase the product.
So the prescription setting actually creates significant barriers and
time delays as we go through the process.
With
that, I'm going to turn the podium over to Dr. Dickerson. Dr. Dickerson is President-elect of the
American College of Obstetricians and Gynecologists. She is the Director of Obstetrics and
Gynecology at the University of California Irvine
Medical Center, and with that, Dr. Dickerson.
DR.
DICKERSON: Good morning. My name is Vivian Dickerson, and I am an
Associate Professor at the University of California-Irvine and Director of the
General OB-GYN Division at UCI Medical Center.
I
have no financial interests or potential conflicts of interest to disclose in
this case.
As
President-elect of the American College of Obstetricians and Gynecologists, I
am representing ACOG in support of over-the-counter status for Plan B. The college rarely presents product specific
testimony. However, we are delighted to
have the opportunity to present today because we strongly believe that Plan B
meets the FDA criteria for over-the-counter status, and because there is a
public health imperative to increase access to emergency contraception.
ACOG's
mission is to improve health care of women.
We pursue that mission through education and advocacy. On behalf of ACOG, a national organization
representing over 45,000 members who provide health care for women, I am
speaking today to encourage the FDA to act favorably and quickly on the Women's
Capitol Corporation/Barr Laboratories application to make Plan B available to
women over the counter.
Plan
B is safe, and it is effective. It is
not teratogenic. It has no potential for
overdose or addiction. It does not
require special medical screening. It is
easy to use, and the labeling instructions are clear and understandable.
We
know that Plan B works. It prevents
pregnancy. By preventing unintended
pregnancy, it also prevents abortion.
We
know that women use it correctly and are very unlikely to substitute it for an
ongoing method of birth control. For
these reasons, ACOG supports the removal of the prescription requirement for
Plan B for all women of reproductive age.